Antidepressant Response of DMT Masked With Propofol (DMT4D)

University Hospital Basel

Status: Enrolling

Conditions: Major Depressive Disorder; Psychedelic Experiences

Treatments: Drug: Placebo; Drug: N,N-Dimethyltryptamine; Procedure: Propofol; Procedure: no sedation

Study type: Interventional

Funder types: Other

Identifiers

NCT06927076

2024-02312 am24Liechti6;

Details and patient eligibility

About

The aim of this study is to elucidate if the anti-depressive effect of N,N-dimethyltryptamine (DMT) is based on a biological mechanisms including neuroplasticity and anti-inflammatory effect or due to the subjective psychedelic experience.

Full description

Major depressive disorder (MDD) affects nearly 20% of people, but current treatments-both pharmacological and psychotherapeutic-have limited efficacy, especially for mild to severe cases. Psychedelics like LSD, psilocybin, and DMT are being explored as alternative therapies, with studies showing promising antidepressant effects. However, it is unclear whether these benefits stem from their acute subjective (psychedelic) experience or from biological mechanisms like neuroplasticity and anti-inflammatory effects.

This study aims to determine if the antidepressant effects of DMT occur independently of its psychedelic experience. To test this, DMT will be administered under sedation (with propofol) to mask subjective effects, as well as without sedation.

Enrollment: 112 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participants must meet DSM-5 criteria for MDD of at least moderate severity (MADRS>20).
2. Participants either currently do not use antidepressants or are treated with a stable dose for at least 4 weeks prior to randomization.
3. Age ≥ 21 years old.
4. Sufficient understanding of the German language.
5. Able to understand the study procedures and risks and willing to adhere to the protocol and sign the consent form.
6. Willing not to drive or operate heavy machinery on the treatment day.
7. Willing to refrain from more than 7 standard alcoholic drinks a week, more than 10 cigarettes a day, more than 2 cups of coffee a day, and any illicit substances during study participation.
8. Willing to use effective contraceptive measures throughout study participation.

Exclusion criteria

1. Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features.
2. First-degree relative with a psychotic or bipolar disorder.
3. Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6).
4. Psychiatric condition judged to be incompatible with establishment of rapport with study team members and/or safe exposure to DMT, e.g. diagnosed or suspected borderline personality disorder.
5. Current post-traumatic stress disorder or acute stress reaction due to a traumatic event.
6. Post-partum depression.
7. Pregnant or breastfeeding women.
8. Current or recent history of significant suicide ideation or suicide behavior within the past 6 months.
9. Current severe substance use disorder other than nicotine.
10. Planned ketamine, other psychedelic, or electroconvulsive treatment or any such treatment within the past 3 months.
11. Any lifetime use of DMT, use of any other psychedelics within last 3 month or lifetime use of any other psychedelics more than 15 times.
12. Patients who are treated with neuroleptics or known antagonists of 5-HT2 receptors or monoamine oxidase inhibitors (MAOI) and are not able/willing to pause.
13. Increased risk for adverse reactions to propofol or soja products.
14. Increased risk for aspiration.
15. Increased risk for difficult mask ventilation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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112 participants in 4 patient groups, including a placebo group

DMT without sedation

Experimental group

Description:

DMT without sedation (propofol)

Treatment:

Procedure: no sedation

Drug: N,N-Dimethyltryptamine

DMT with sedation

Experimental group

Description:

DMT with sedation (propofol)

Treatment:

Procedure: Propofol

Drug: N,N-Dimethyltryptamine

Placebo without sedation

Placebo Comparator group

Description:

Placebo (double-blind) without sedation (propofol)

Treatment:

Procedure: no sedation

Drug: Placebo

Placebo with sedation

Placebo Comparator group

Description:

Placebo (double-blind) with sedation (propofol)

Treatment:

Procedure: Propofol

Drug: Placebo